Abstract: We often say “cytokine storm”, which is actually a very horrible word. So exactly what is a cytokine storm? And listen to me slowly. Cytokine storm refers to the phenomenon that the immune system is over-activated after the body infects microorganisms or in other cases, resulting in the rapid and massive production of various cytokines in body fluids. These cytokines include TNF-α, IL-1, IL-6, IL-12, and IFN-α, IFN-β, IFN-γ, MCP-1, IL-8 and the like. In patients with tumors with impaired immune function, a fatal cytokine storm caused by the disease itself, treatment plan or supportive treatment may occur. Cytokine storms are also common in some viral infections, such as avian influenza, influenza, certain medications, such as certain cytokines, monoclonal antibodies, and chemotherapeuticsand hematopoietic disorders, such as graft resistance after bone marrow transplantation. Cytokine storm is an important cause of acute respiratory distress syndrome (ARDS) and multiple organ failure, and it is one of the important causes of death in many diseases, and has recently attracted more and more attention.

Keywords: cytokine storm, infection, immune system

Relationship between cytokine storm and immune system

The daily work of the immune system is to clear the infection, but if the immune system is activated to the limit or loses control, it will harm the host, and the extreme immune attack is "cytokine storm." In the final stage of Ebola virus infection, cytokine storm is the killer. Like many viruses like avian flu and SARS, it can trigger a fierce attack on the body by the immune system.

Immune cells communicate with each other through cytokines, which are small molecules that are released into the bloodstream by the cells, allowing immune cells to rush to the site of infection;phagocytosis damaged cells, and even penetrates the walls of blood vessels. Cytokines can also cause inflammation, swelling, fever, and pain in the damaged body.

Cytokine storm is a help-seeking signal that is designed to give the immune system a full turn of time. This last resort suicide attack can damage the virus, but it will also leave a lot of damage. The blood vessels have suffered the most important offensive. Cytokine storms make the blood vessel walls easier to penetrate. As a result, arteries, veins, and capillaries begin to exude blood and plasma.

Cytokine storms also trigger large releases of nitric oxide. This substance will further dilute the blood and destroy the blood vessels. All of these factors combine to lower blood pressure to dangerous levels, so the patient does not die from blood loss, but rather dies from something like severe septic shock. The Ebola virus immediately targets and infects cells of the immune system, one of which is dendritic cells. It will quietly sneak into the interior of dendritic cells, essentially turning off their alarm system. So the immune system is not aware that it should make antibodies against Ebola, which is the horrible thing about cytokine storms.

Relationship between cytokine storm and infection

When a tissue is injured or infected, the inflammatory response is the primary response of the body. The inflammatory response activates innate and adaptive immune responses and solves problems and restores homeostasis through this response. Inflammation is easier to distinguish because of its distinctive features (fever, redness, swelling, and pain). The classic self-limiting inflammatory response has four distinct periods:

*Identifying the problem

*Assembling white blood cells and other immune system components

*Identifying and eliminating threats

*Restoring homeostasis

In the case of infection, pathogens try to disrupt the sophisticated immune mediation system to evade the immune response, and evolve a variety of escape strategies to facilitate their survival and growth. In some cases, the pathogen can escape the immune response and thus not induce an effective immune response; in other cases, certain pathogens can excessively stab the immune system, which can cause tissue damage, such as local necrosis, a potentially fatal threat. . Many studies have focused on how pathogens do not escape immune responses, and diseases caused by cytokine storms have gradually gained attention in recent years. Studies have found that for diseases caused by certain pathogens, when the body's immunity is increased by adding drugs or other means, it is often impossible to effectively control the disease, and even further increase the threat of cytokine storms, which may lead to a more serious condition must occur, which must be noted.

High fever must be a bad thing?

Actually, high fever caused by cytokine storms may not be a bad thing.

Now we know that fever is an important method used by the immune system against foreign infections. Its purpose is to accelerate the body's body temperature and accelerate various physiological activities, including the rapid growth and division of immune cells, in order to respond to the crisis. From the discovery of "invaders" from immune cells to the "combat state" of the body as a whole, this process is coordinated through a series of protein factors. These factors are sometimes referred to as "inflammatory factors" and are sometimes referred to as "cytokines."

The various cellular cytokines currently used clinically, as well as recently approved antibodies for activating immune cells, are much more potent than the use of a single cytokine. The release of cytokines is so strong that in a common immune response, the immune system may release more than 100 cytokines. If the immune system is strongly stimulated, a large number of cytokines are released into the blood in a short period of time, causing a so-called "cytokine storm." The clinical consequences of "cytokine storm" are very serious, including "high fever." Although "cytokine storm" is a new concept, this storm does not occur only in immunotherapy. Many diseases, including influenza and sepsis, can cause "cytokine storms." The difference is that in cancer immunotherapy, moderate and controllable "high fever" is the necessary effect of treatment. From this point of view, sometimes a high fever is not necessarily a bad thing.

 References

[1] Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature, 2007, 449(7164):819-825

[2] Tisoncik JR, Korth MJ, Simmons CP, et al. Into the eye of the cytokine storm. Microbiol Mol Biol Rev, 2012, 76(1):16-33